Author + information
- Received June 6, 2017
- Revision received July 25, 2017
- Accepted July 27, 2017
- Published online December 25, 2017.
- Walter J. Paulus, MD, PhD∗ ( and )
- Elisa Dal Canto, MD
- ↵∗Address for correspondence:
Prof. Dr. Walter J. Paulus, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, O|2 building 10W13, De Boelelaan 1118, 1081 HV Amsterdam, the Netherlands.
Noncardiac comorbidities such as diabetes mellitus (DM) have different outcomes in heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). These different outcomes are the result of distinct myocardial effects of DM on HFpEF and HFrEF, which relate to different mechanisms driving myocardial remodeling in each heart failure phenotype. Myocardial remodeling is driven by microvascular endothelial inflammation in HFpEF and by cardiomyocyte cell death in HFrEF. Evidence consists of: different biomarker profiles, in which inflammatory markers are prominent in HFpEF and markers of myocardial injury or wall stress are prominent in HFrEF; reduced coronary flow reserve with microvascular rarefaction in HFpEF; and upregulation of free radical-producing enzymes in endothelial cells in HFpEF and in cardiomyocytes in HFrEF. As biopsies from patients with diabetic cardiomyopathy reveal, DM affects failing myocardium by phenotype-specific mechanisms. In HFpEF, DM mainly increases cardiomyocyte hypertrophy and stiffness, probably because of hyperinsulinemia and microvascular endothelial inflammation. In HFrEF, DM augments replacement fibrosis because of cardiomyocyte cell death induced by lipotoxicity or advanced glycation end products. Because DM exerts distinct effects on myocardial remodeling in HFpEF and HFrEF, the heart failure phenotype is important for DM therapy.
Dr. Paulus is supported by grants from Cardiovasculair Onderzoek Nederland, Dutch Heart Foundation. Dr. Dal Canto has reported she has no relationships relevant to the contents of this paper to disclose.
- Received June 6, 2017.
- Revision received July 25, 2017.
- Accepted July 27, 2017.
- 2018 American College of Cardiology Foundation